OBJECTIVE: To examine placental growth factor (PlGF) levels in first trimester maternal serum in trisomy 21 pregnancies and to investigate the potential value of PlGF in a first trimester screening test. METHODS: First trimester maternal serum from 70 trisomy 21 cases and 375 euploid controls were retrospectively analyzed for PlGF using a DELFIA Xpress immunoassay platform. Results were expressed as multiples of medians (MoM) for comparison. RESULTS: PlGF levels were significantly decreased in pregnancies with trisomy 21, 0.76 MoM versus 0.98 MoM in controls. Inclusion of PlGF into the first trimester combined test [maternal age, pregnancy associated plasma protein-A (PAPP-A), free-beta human chorionic gonadotrophin (beta-hCG) and nuchal translucency] would increase the detection rate by 0.5% at a 5% false positive rate. CONCLUSION: PlGF at 11 weeks to 13 weeks 6 days has the potential to be included as a marker for the detection of pregnancies with trisomy 21.